Cinnamtannin B-1, a natural antioxidant that reduces the effects of H(2)O(2) on CCK-8-evoked responses in mouse pancreatic acinar cells.

This work was designed in order to gain an insight on the mechanisms by which antioxidants prevent pancreatic disorders. We have examined the properties of cinnamtannin B-1, which belongs to the class of polyphenols, against the effect of hydrogen peroxide (H(2)O(2)) in mouse pancreatic acinar cells. We have studied Ca(2+) mobilization, oxidative state, amylase secretion, and cell viability of cells treated with cinnamtannin B-1 in the presence of various concentrations of H(2)O(2). We found that H(2)O(2) (0.1-100 μM) increased CM-H(2)DCFDA-derived fluorescence, reflecting an increase in oxidation. Cinnamtannin B-1 (10 μM) reduced H(2)O(2)-induced oxidation of CM-H(2)DCFDA. CCK-8 induced oxidation of CM-H(2)DCFDA in a similar way to low micromolar concentrations of H(2)O(2), and cinnamtannin B-1 reduced the oxidant effect of CCK-8. In addition, H(2)O(2) induced a slow and progressive increase in intracellular free Ca(2+) concentration ([Ca(2+)](c)). Cinnamtannin B-1 reduced the effect of H(2)O(2) on [Ca(2+)](c), but only at the lower concentrations of the oxidant. H(2)O(2) inhibited amylase secretion in response to cholecystokinin, and cinnamtannin B-1 reduced the inhibitory action of H(2)O(2) on enzyme secretion. Finally, H(2)O(2) reduced cell viability, and the antioxidant protected acinar cells against H(2)O(2). In conclusion, the beneficial effects of cinnamtannin B-1 appear to be mediated by reducing the intracellular Ca(2+) overload and intracellular accumulation of digestive enzymes evoked by ROS, which is a common pathological precursor that mediates pancreatitis. Our results support the beneficial effect of natural antioxidants in the therapy against oxidative stress-derived deleterious effects on cellular physiology.